Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract.
Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract.
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DOI：
10.1038/ki.2014.268
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发表时间：
2015-01
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
最近的证据表明抗菌肽可以保护尿路免受感染。核糖核酸酶 7 (RNase 7) 是 RNase A 超家族的成员，是一种有效的上皮衍生蛋白，可维持人类尿道不育。 RNase 7 表达仅限于灵长类动物，限制了对其体内抗菌活性的评估。在这里，我们将核糖核酸酶 6 (RNase 6) 鉴定为人类和小鼠中存在的 RNase A 超家族成员，相对于 RNase 7，其在氨基酸水平上最为保守。与 RNase 7 一样，重组人和鼠 RNase 6 对尿路病原体具有有效的抗菌活性。实时定量 PCR 和免疫印迹分析表明，感染期间人和小鼠泌尿道中的 RNase 6 mRNA 和蛋白质上调。免疫染色将 RNase 6 定位于驻留和浸润的单核细胞、巨噬细胞和中性粒细胞。泌尿道致病性大肠杆菌可诱导人 CD14+ 单核细胞和鼠骨髓来源的巨噬细胞表达 RNase 6 肽。因此，RNase 6 是一种诱导型骨髓源性蛋白质，其表达与上皮源性 RNase 7 明显不同，但具有同样有效的抗菌活性。我们的研究表明 RNase 6 作为一种进化上保守的抗菌肽，参与维持尿道不育。
Recent evidence suggests antimicrobial peptides protect the urinary tract from infection. Ribonuclease 7 (RNase 7), a member of the RNase A superfamily, is a potent epithelial-derived protein that maintains human urinary tract sterility. RNase 7 expression is restricted to primates, limiting evaluation of its antimicrobial activity in vivo. Here we identified Ribonuclease 6 (RNase 6) as the RNase A Superfamily member present in humans and mice that is most conserved at the amino acid level relative to RNase 7. Like RNase 7, recombinant human and murine RNase 6 has potent antimicrobial activity against uropathogens. Quantitative real-time PCR and immunoblot analysis indicate that RNase 6 mRNA and protein are up-regulated in the human and murine urinary tract during infection. Immunostaining located RNase 6 to resident and infiltrating monocytes, macrophages, and neutrophils. Uropathogenic E. coli induces RNase 6 peptide expression in human CD14+ monocytes and murine bone marrow derived macrophages. Thus, RNase 6 is an inducible, myeloid-derived protein with markedly different expression from the epithelial-derived RNase 7 but with equally potent antimicrobial activity. Our studies suggest RNase 6 serves as an evolutionarily conserved antimicrobial peptide that participates in the maintenance of urinary tract sterility.
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影响因子：
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